The S107 BALB/c plasmacytoma tumor produces an IgA myeloma protein which has specificity for the hapten phosphorylcholine (PC). The idiotype of this protein is shared by several other BALB/c myeloma proteins and represents the major subgroup of PC-binding myeloma proteins. This idiotype also is the major idiotype of anti-PC antibodies induced in BALB/c mice by immunization with PC-antigens. We have cloned in soft agar several sublines from an in vitro adapted S107 line by overlay with heterologous anti-S107 sera and PC-antigen. These sublines differ in the density of idiotype on cell surface and the amount of idiotype secreted. The aim of this study is to use the surface idiotypes as target for selecting idiotype variant clones by the criteria of an altered reactivity with anti-idiotypic antibody. The first step towards this goal is the development of monospecific antibodies against idiotypic determinants. Lymph node cells and spleen cells of A and BALB/c mice immunized against S107 idiotype will be fused with P3 x 63 Ag8 cells. Positive cultures will be screened for anti-S107 antibody secretion using a RIA for anti-S107. We propose to use complement-mediated cytotoxicity and fluorescence activated cell sorting to select clones which are idiotype negative. Immunoglobulin secreted by these variant clones will be analysed by isoelectric focusing and PAGE in SDS. Clones secreting a protein indicative for minimal structural alterations will be grown in vivo. Enough material will be collected for sequence analysis and comparison of the variant structure with the parental S107 protein. It is hoped that the study of idiotype variants will provide new insight into the structure-function relationship of idiotype and specificity and provide further clues for the mechanisms generating antibody diversity.